De novo sequencing of peptides on single resin beads by MALDI-FTICR tandem mass spectrometry

J Am Soc Mass Spectrom. 2010 Feb;21(2):215-9. doi: 10.1016/j.jasms.2009.10.004. Epub 2009 Oct 12.


An efficient approach in combinatorial chemistry is the synthesis of one-bead-one-compound peptide libraries. In contrast to synthesis and functional screening, which is performed in a largely automated manner, structure determination has been frequently laborious and time-consuming. Here we report an approach for de novo sequencing of peptides on single beads by matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance (MALDI-FTICR) tandem mass spectrometry, using a resin with a photolinker for solid-phase peptide synthesis. Upon sorting out single beads, an efficient sample preparation on the MALDI target was developed that enables fragmentation upon irradiation of the bead-matrix mixture with the ultraviolet (UV)-MALDI laser, with enhanced yield of sequence-specific fragment ions at increased laser energy. This approach is illustrated by sequence determinations of two peptides from a library with sequences varying in a single amino acid; the feasibility with tandem-MS procedures and fragment ion assignment was ascertained by sustained off-resonance irradiation/collision induced dissociation (SORI/CID) and infrared multiphoton dissociation (IRMPD) fragmentation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fourier Analysis*
  • Peptide Library
  • Peptides / analysis
  • Peptides / chemistry*
  • Sequence Analysis, Protein / methods*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*
  • Tandem Mass Spectrometry / methods*


  • Peptide Library
  • Peptides